Promising results from prophylactic HPV vaccine trials support using these vaccines in cervical cancer prevention programs in the-future. Since vaccine coverage rarely if ever reaches 100%, population-level effectiveness of a prophylactic vaccine designed to prevent a sexually transmitted infection, such as an HPV vaccine, depends not only on the efficacy of the vaccine, but also on the incidence and duration of infection in both men and women. Although much has been learned about the epidemiology of human papillomavirus (HPV) infections in women, little is known about the incidence, determinants, and natural history of HPV infections in men. Research in men has been hampered, in part, by an inability to obtain adequate genital samples for HPV DNA testing. As discussed in this proposal, we developed a sensitive and acceptable method for sample collection and now propose to use this method in a prospective natural history study with the following aims. Among young men, (1) determine the incidence of infection with any type of HPV, oncogenic HPV, specific HPV types including HPV 16 and HPV6/11, and HPV 16 variants;(2) define risk 'factors for incident HPV infection, including lifetime and recent number of sex partners, circumcision status, condom use, frequency of vaginal intercourse, and courtship behavior;and (3) describe the natural history of HPV infection in men as measured by duration and levels of HPV DNA, HPV type-specific seroconversion, duration of antibodies, and development of genital warts. Our long-term goal is development of cost-effective approaches to the prevention of HPV-related cancers.